CMOS-based multielectrode array for spatially controlled single-cell gene editing and monitoring

I will exploit a novel CMOS microelectrode array chip (MEA) to monitor and genetically modify cells at the single-cell level. First, I will use impedance measurements and cell imaging to identify cell types with distinct functional properties (e.g. proliferation rate, impedance signatures) from heterogeneous glioblastoma models. Second, I will locally electroporate cells to fluorescently tag them and genetically edit their genome, while observing their oncogenic potential. Experiments will be guided by and complemented with modeling and simulation approaches to gain a deeper understanding of the physical basis underlying the empirical observations. I chose glioblastoma (GBM) as a model system for understanding factors that affect single-cell electroporation and monitoring. GBM is the most aggressive adult brain malignancy and is largely incurable. GBM exhibits substantial cell-to-cell variation, which is a major contributor to complications in diagnosis and treatment. Treatment options remain limited and inefficient, mostly due to the presence of resistant tumor cell subpopulations. The functional properties and clinical relevance of each of these subtypes remain largely understudied, in part because appropriate technologies to study heterogeneous cell populations are lacking. I believe our advanced CMOS MEA can solve this problem. If successful, this technology will uniquely enable us to elucidate functional cell heterogeneity in cancer, leading to better treatment options.